Serous fluid cytology of multicentric Castleman’s disease and other lymphoproliferative disorders associated with Kaposi sarcoma‐associated herpes virus: a review with case reports

C. Lobo, S. Amin, A. Ramsay, T. Diss and G. Kocjan Serous fluid cytology of multicentric Castleman’s disease and other lymphoproliferative disorders associated with Kaposi sarcoma‐associated herpes virus: a review with case reports Objective: The aim of this study is to describe and review the cytological features of Kaposi sarcoma‐associated herpes virus (KSHV) related entities, such as multicentric Castleman’s disease (MCD), plasmablastic‐lymphoma (PBL) and primary effusion lymphoma (PEL), which all may present as body cavity effusions. Serous fluid cytology of MCD and PBL has not, to our knowledge, thus far been described. Although different in nature, MCD, PBL and PEL are characterized by similar morphological features. Materials and methods: Body cavity effusions from four different patients with previously known or unknown KSHV‐related lymphoproliferations have been examined by routine cytology, immunocytochemistry (IC) and polymerase chain reaction (PCR). Results: MCD, PBL and PEL are all characterized by increased cellularity, comprising mainly lymphoid and plasmacytoid cells with variable proportions of immunoblasts. Immunocytochemistry and PCR results show the MCD to be CD138 and KSHV positive, CD30 negative, IgM, IgH and lambda restricted but IgH polyclonal. PBL was CD138 positive, kappa restricted, weakly positive with VS38 and over 80% positive with MIB 1. PEL was CD45, EMA, CD138, KSHV, p53 and CD3 positive, CD20, EBV, CD30, CD2, CD4, ALK1, epithelial and mesothelial markers negative, and PCR monoclonal B‐cell expanded (Ig‐kappa bands). Conclusion: Cytological examination of effusions in KSHV‐related lymphoproliferative disorders may show similar morphological features but clonality studies and immunocytochemistry are very helpful in distinguishing between these rare benign and malignant lymphoproliferative diseases.     

Highly selective fusion and accumulation of hybrid liposomes into primary effusion lymphoma cells along with induction of apoptosis

Primary effusion lymphoma (PEL) is an aggressive neoplasm caused by human herpes virus-8 infection, and is generally resistant to chemotherapy. Hybrid liposomes, composed of dimyristoylphosphatidylcholine (DMPC) and polyoxyethylene (21) dodecyl ether (C₁₂(EO)₂₁) (HL-21), were rapidly accumulated in the membrane of PEL cells. HL-21 also increased membrane fluidity of PEL cells, and induced caspase-3 activation along with cell death. These results suggest that HL-21 should be an effective and attractive regent for PEL treatment.     

Role of svp in Drosophila Pericardial Cell Growth

The Drosophila dorsal vessel is a segmentally repeated linear organ, in which seven-up (svp) is expressed in two pairs of cardioblasts and two pairs of pericardial cells in each segment. Under the control of hedgehog (hh) signaling from the dorsal ectoderm, svp participates in diversifying cardioblast identities within each segment. In this experiment, the homozygous embryos of svp mutants exhibited an increase in cell size of Eve positive pericardial cells (EPCs) and a disarranged expression pattern, while the cardioblasts pattern of svp-lacZ expression was normal. In the meantime, the DA1 muscle founders were absent in some segments in svp mutant embryos, and the dorsal somatic muscle patterning was also severely damaged in the late stage mutant embryos, suggesting that svp is required for the differentiation of Eve-positive pericardial cells and DA1 muscle founders and may have a role in EPC cell growth.     

Sodium butyrate induces apoptosis and cell cycle arrest in primary effusion lymphoma cells independently of oxidative stress and p21CIP1/WAF1 induction

Primary effusion lymphoma, a peculiar type of B cell non-Hodgkin lymphoma, preferentially develops in immunodeficient individuals and its pathogenesis is closely linked with human herpesvirus 8 (HHV-8). HHV-8 is present primarily persistence in primary effusion lymphoma cells, and the lytic cycle of HHV-8 can be induced by sodium butyrate (NaB) treatment. HHV-8 gene expression is affected by NaB in BCBL-1 cells, but the cellular response of BCBL-1 cells upon NaB treatment has not been investigated to date. Using BCBL-1 cells, a HHV-8 harboring cell line, we demonstrated that sodium butyrate could induce the reactive oxygen species generation, apoptosis and cell cycle arrest in BCBL-1 cells. The sodium butyrate-induce cell cycle arrest was associated with the decrease of Cdc2, Cdk4 and cyclin A in BCBL-1 cells without altering the protein levels of p21^CIP1/WAF1. The apoptosis induced by sodium butyrate in BCBL-1 cells was independent of oxidative stress. (Mol Cell Biochem xxx: 1–9, 2005)     

Axial complex of Crinoidea: Comparison with other Ambulacraria

The anatomy of Crinoidea differs from that of the other modern echinoderms. In order to see, whether such differences extend to the axial complex as well, we studied the axial complex of Himerometra robustipinna (Himerometridae, Comatulida) and compared it with modern Eleutherozoa. The axial coelom is represented by narrow spaces lined with squamous coelothelium, and surrounds the extracellular haemocoelic lacunae of the axial organ. The latter is located, for the most part, along the central oral-aboral axis of the body. The axial organ can be divided into the lacunar and tubular region. The tubular coelomic canals penetrating the thickness of the axial organ have cuboidal epithelial lining, and end blindly both on the oral and aboral sides. The axial coelom, perihaemal coelom, and genital coelom are clearly visible, but they connect with the general perivisceral coelom and with each other via numerous openings. The haemocoelic spaces of the oral haemal ring pass between the clefts of the perihaemal coelom, and connect with the axial organ. In addition, the axial organ connects with intestinal haemal vessels and with the genital haemal lacuna. Numerous thin stone canaliculi pierce the spongy tissue of the oral haemal ring. They do not connect with the environment. On the oral side, each stone canaliculus opens into the water ring. The numerous slender tegmenal pores penetrate the oral epidermis of the calyx and open to the environment. Tegmenal canaliculi lead into bubbles of the perivisceral coelom. Some structures of the crinoid axial complex (stone canaliculi, communication between different coeloms) are numerous whereas in other echinoderms these structures are fewer or only one. The arrangement of the circumoral complex of Crinoidea is most similar to Holothuroidea. The anatomical structure and histology of the axial complex of Crinoidea resembles the “heart-kidney” of Hemichordata in some aspects.     

Unintended Harm and Benefit of the Implantable Defibrillator in an Unfortunate 19-Year-Old Male: Featuring a Sequence of Rare Life-threatening Complications of Cardiac Procedures

All procedures have inherent risk. Our patient endured a sequence of rare life-threatening complications from commonly preformed procedures. The sequence of these complications was; large pericardial effusion post implantable cardioverter-defibrillator (ICD) implantation with echocardiographic signs of tamponade, left main narrowing post radiofrequency ablation, and late stent thrombosis post coronary intervention with a bare metal stent. All these occurred to one unfortunate young man. Furthermore, our patient demonstrated an unintended benefit of ICD which saved his life.     

Prognostic values of VEGF and IL-8 in malignant pleural effusion in patients with lung cancer

Abstract

Objective: The aim of this study was to evaluate the prognostic value of VEGF and IL-8 in pleural effusion in patients with lung cancer.

Materials and method: Commercially available ELISA was used to determine VEGF and IL-8 levels.

Results: The level of VEGF showed significant correlations with lymph node metastasis and distant metastasis. But, IL-8 was only correlated with lymph node metastasis. Univariate and multivariate analysis revealed elevated VEGF level was an independent predictor of shorter OS and DFS.

Conclusion: VEGF could be an important component that contributes to pleural effusion formation, and an important prognostic factor for lung cancer.     

Pyrrolidinium fullerene induces apoptosis by activation of procaspase-9 via suppression of Akt in primary effusion lymphoma

Primary effusion lymphoma (PEL) is a subtype of non-Hodgkin’s B-cell lymphoma and is an aggressive neoplasm caused by Kaposi’s sarcoma-associated herpesvirus (KSHV) in immunosuppressed patients. In general, PEL cells are derived from post-germinal center B-cells and are infected with KSHV. To evaluate potential novel anti-tumor compounds against KSHV-associated PEL, seven water-soluble fullerene derivatives were evaluated as potential drug candidates for the treatment of PEL. Herein, we discovered a pyrrolidinium fullerene derivative, 1,1,1′,1′-tetramethyl [60]fullerenodipyrrolidinium diiodide, which induced apoptosis of PEL cells via a novel mechanism, the caspase-9 activation by suppressing the caspase-9 phosphorylation, causing caspase-9 inactivation. Pyrrolidinium fullerene treatment reduced significantly the viability of PEL cells compared with KSHV-uninfected lymphoma cells, and induced the apoptosis of PEL cells by activating caspase-9 via procaspase-9 cleavage. Pyrrolidinium fullerene additionally reduced the Ser473 phosphorylation of Akt and Ser196 of procaspase-9. Ser473-phosphorylated Akt (i.e., activated Akt) phosphorylates Ser196 in procaspase-9, causing inactivation of procaspase-9. We also demonstrated that Akt inhibitors suppressed the proliferation of PEL cells compared with KSHV-uninfected cells. Our data therefore suggest that Akt activation is essential for cell survival in PEL and a pyrrolidinium fullerene derivative induced apoptosis by activating caspase-9 via suppression of Akt in PEL cells. In addition, we evaluated whether pyrrolidinium fullerene in combination with the HSP90 inhibitor (geldanamycin; GA) or valproate, potentiated the cytotoxic effects on PEL cells. Compared to treatment with pyrrolidinium fullerene alone, the addition of low-concentration GA or valproate enhanced the cytotoxic activity of pyrrolidinium fullerene. These results indicate that pyrrolidinium fullerene could be used as a novel therapy for the treatment of PEL.     

Eosinophilic Pleuritis due to Sparganum: A Case Report

Sparganosis is a rare parasitic disease caused by migrating plerocercoid tapeworm larva of the genus Spirometra. Infection in humans is mainly caused by the ingestion of raw or inadequately cooked flesh of infected frogs, snakes, and chickens. Here, we report a rare case of a 45-year-old man who was admitted to our hospital with left lower chest pain. The chest radiograph and computed tomography (CT) scan revealed localized pleural effusion in the left lower lobe; further, peripheral blood eosinophilia and eosinophilic pleural effusion were present. Percutaneous catheter drainage was performed, which revealed long worm-shaped material that was identified as a sparganum by DNA sequencing. The patient showed clinical improvement after drainage of the sparganum. This study demonstrates the importance of considering parasitic diseases in the differential diagnosis of eosinophilic pleural effusion.